Congestive heart failure (CHF) affects over 5 million Americans and is a major cause of death and the most common reason for hospitalization. Nearly fifty percent of CHF patients will die within 5 years of diagnosis, which is a higher mortality than most forms of cancer. Cardiac resynchronization therapy (CRT) has emerged as a promising therapy for CHF patients with dyssynchrony and has been shown in trials to significantly improve symptoms and cardiac pump efficiency when pacemaker leads are placed successfully. Today, X-ray imaging alone is used to guide placement of pacemaker leads for CRT, but this modality provides little functional and anatomic information to the physician. Lead placement is performed by steering relatively "blindly" which contributes to a procedural failure rate of 20% and may explain a non-response rate of more than 30%. On the other hand, MRI offers unique soft tissue contrast without the use of ionizing radiation for depicting coronary vein morphology, quantifying myocardial dyssynchrony, and identifying scar tissue. It is widely believed that these elements are key determinants of clinical outcomes for CRT and that they should be used for patient selection, procedural planning, and guidance of CRT. The objective of this project is to develop an "X-ray fused with MR" (XFM) image guidance system for integrating pre-procedural MR-derived vein imaging, mechanical dyssynchrony and myocardial viability with intra-procedural X-ray images to guide CRT procedures. These measures will allow the physician to directly relate the positions of the coronary vein and left ventricular leads with the surrounding soft tissue characteristics in real-time during lead placement. We hypothesize that this XFM guidance system will facilitate more effective placement of the pacemaker leads, ultimately leading to an increase in CRT responder rates. This project will be divided into three main Specific Aims: (1) to develop a cardiac MR imaging methodology for creating a single 3D representation of coronary vein anatomy, mechanical dyssynchrony, and myocardial viability (2) to develop an XFM interventional guidance system that provides real-time overlay of MR derived measures on live X-ray images with compensation of respiratory motion in the EP lab (3) to validate XFM CRT system with in vivo animal experiments followed by first in human clinical study. This project will bring together unique MR imaging methods and state of the art interventional image guidance to address one of the leading causes of death in the United States. PUBLIC HEALTH RELEVANCE: Congestive heart failure (CHF) affects over 5 million Americans and is a major cause of death and the most common reason for hospitalization. Cardiac resynchronization therapy (CRT) has emerged as a promising therapy for CHF patients with dyssynchrony and has been shown in trials to significantly improve symptoms and cardiac pump efficiency when pacemaker leads are placed successfully. Today, X-ray imaging alone is used to guide placement of pacemaker leads for CRT, but this modality provides little functional and anatomic information to the physician, which may explain a non-response rate of more than 30%. The objective of this project is to develop an "X-ray fused with MR" (XFM) image guidance system for integrating pre-procedural MRI-derived vein imaging, mechanical dyssynchrony and myocardial viability with intra- procedural X-ray images to guide CRT procedures, with the goal of improving patient response rates.